We have established a mouse model for examining several basic questions about the role of acute phase reactants (APR) in nonspecific host resistance. The model is based on serum amyloid P-component (SAP), the major acute phase reactant of mice, which is a molecular homologue of C-reactive protein (CRP), the prototype APR in humans. Methods for purification and quantitation (ELISA) of mouse SAP have been developed. The mouse strain variation in the endogenous level of SAP and the extent of the response have allowed us to map the gene controlling SAP levels to chromosome 1 with close linkage to the Ly-9, M1s, and H-25 loci. A congenic strain for the BALB/c H-25 locus, which is on the low SAP background, C57BL/6ByJ, is being used to study the role of SAP in resistance to microbial and viral infections. The in vitro induction and synthesis of SAP by mouse hepatocytes is driven primarily by IL-1 but is enhanced by another monokine. Hepatocyte recruitment into new SAP synthesis is observed in co-cultures of hepatocytes with macrophages and/or IL-1 when measured by limiting dilution analysis of hepatocytes. Purified mouse SAP is a potent inducer of additional IL-1 production by elicited macrophages. One consequence of this activity is that SAP enhances IgG production in vitro in response to T-dependent antigens. APRs that arise during an inflammatory response may not only contribute to nonspecific host resistance but also may enhance subsequent specific immunity. (HF)